De novo double mutation in PAX6 and mtDNA tRNA Lys associated with atypical aniridia and mitochondrial disease

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 85; no. 2; pp. 163 - 168
• Main Authors: Brinckmann, Anja, Rüther, Klaus, Williamson, Kathleen, Lorenz, Birgit, Lucke, Barbara, Nürnberg, Peter, Trijbels, Frans, Janssen, Antoon, Schuelke, Markus
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01.02.2007
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-006-0112-y

We report on the clinical, molecular and biochemical findings of a patient with the rare event (<4.02 × 10-9 per generation) of coinciding de novo mutations in the nuclear PAX6 (c.1252-1267del16) and the mitochondrial mt.RNA Lys (8347A[arrow right]G) genes. The boy suffers from exercise intolerance, ptosis, nystagmus, macular hypoplasia and anterior segment abnormalities evocative of Axenfeld-Rieger anomaly. The PAX6 mutation is predicted to cause haploinsufficiency. The novel mt.RNA Lys mutation is located close to the classic myoclonic epilepsy with ragged-red-fibers mutation, but the patient exhibits neither myoclonic epilepsy nor ragged-red-fibers. The degree of mutant mtDNA heteroplasmy, as determined by a very accurate pyrosequencing assay, varies between 31% (muscle) and 38% (fibroblasts). We discuss a potential effect of the PAX6 mutation on the mtDNA mutation rate.